Human Gene MED12 (ENST00000374080.8) from GENCODE V44
  Description: Homo sapiens mediator complex subunit 12 (MED12), mRNA. (from RefSeq NM_005120)
RefSeq Summary (NM_005120): The initiation of transcription is controlled in part by a large protein assembly known as the preinitiation complex. A component of this preinitiation complex is a 1.2 MDa protein aggregate called Mediator. This Mediator component binds with a CDK8 subcomplex which contains the protein encoded by this gene, mediator complex subunit 12 (MED12), along with MED13, CDK8 kinase, and cyclin C. The CDK8 subcomplex modulates Mediator-polymerase II interactions and thereby regulates transcription initiation and reinitation rates. The MED12 protein is essential for activating CDK8 kinase. Defects in this gene cause X-linked Opitz-Kaveggia syndrome, also known as FG syndrome, and Lujan-Fryns syndrome. [provided by RefSeq, Aug 2009].
Gencode Transcript: ENST00000374080.8
Gencode Gene: ENSG00000184634.17
Transcript (Including UTRs)
   Position: hg38 chrX:71,118,596-71,142,450 Size: 23,855 Total Exon Count: 45 Strand: +
Coding Region
   Position: hg38 chrX:71,118,755-71,142,218 Size: 23,464 Coding Exon Count: 45 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesGeneReviewsMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chrX:71,118,596-71,142,450)mRNA (may differ from genome)Protein (2177 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards
HGNCHPRDLynxMalacardsMGImyGene2
neXtProtOMIMPubMedReactomeUniProtKBWikipedia
BioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: MED12_HUMAN
DESCRIPTION: RecName: Full=Mediator of RNA polymerase II transcription subunit 12; AltName: Full=Activator-recruited cofactor 240 kDa component; Short=ARC240; AltName: Full=CAG repeat protein 45; AltName: Full=Mediator complex subunit 12; AltName: Full=OPA-containing protein; AltName: Full=Thyroid hormone receptor-associated protein complex 230 kDa component; Short=Trap230; AltName: Full=Trinucleotide repeat-containing gene 11 protein;
FUNCTION: Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. This subunit may specifically regulate transcription of targets of the Wnt signaling pathway and SHH signaling pathway.
SUBUNIT: Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. Also interacts with CTNNB1 and GLI3.
SUBCELLULAR LOCATION: Nucleus (Probable).
TISSUE SPECIFICITY: Ubiquitous.
DISEASE: Defects in MED12 are the cause of Opitz-Kaveggia syndrome (OKS) [MIM:305450]; also known as FG syndrome type 1 (FGS1) or FG syndrome (FGS). OKS is an X-linked disorder characterized by mental retardation, relative macrocephaly, hypotonia and constipation.
DISEASE: Defects in MED12 are the cause of Lujan-Fryns syndrome (LUJFRYS) [MIM:309520]; also known as X-linked mental retardation with marfanoid habitus. Clinically, Lujan-Fryns syndrome can be distinguished from Opitz-Kaveggia syndrome by tall stature, hypernasal voice, hyperextensible digits and high nasal root.
SIMILARITY: Belongs to the Mediator complex subunit 12 family.
SEQUENCE CAUTION: Sequence=AAD22033.1; Type=Erroneous initiation;
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/MED12";

-  Primer design for this transcript
 

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-  MalaCards Disease Associations
  MalaCards Gene Search: MED12
Diseases sorted by gene-association score: opitz-kaveggia syndrome* (1702), ohdo syndrome, x-linked* (1580), lujan-fryns syndrome* (1252), lujan syndrome* (518), imperforate anus* (404), ohdo syndrome, maat-kievit-brunner type* (400), focal segmental glomerulosclerosis* (289), corpus callosum, agenesis of, with facial anomalies and cerebellar ataxia* (283), corpus callosum agenesis* (283), alacrima, achalasia, and mental retardation syndrome* (163), med12-related disorders* (100), intellectual disability* (93), ohdo syndrome (47), fryns syndrome (35), myoma (12), uterine benign neoplasm (12), reproductive organ benign neoplasm (12), breast fibroadenoma (11), spontaneous ocular nystagmus (11), bacillary angiomatosis (10), uterine fibroid (10), leiomyomatosis (9), bizarre leiomyoma (8), blepharophimosis (7), benign breast phyllodes tumor (7), vestibular nystagmus (7), breast benign neoplasm (6), thoracic benign neoplasm (6), leiomyosarcoma (6), shprintzen-goldberg syndrome (5), x-linked non-specific intellectual disability* (4), schizophrenia (2)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 19.62 RPKM in Ovary
Total median expression: 477.47 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -52.30159-0.329 Picture PostScript Text
3' UTR -63.00232-0.272 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR019035 - Mediator_Med12
IPR021989 - Mediator_Med12_catenin-bd
IPR021990 - Mediator_Med12_LCEWAV

Pfam Domains:
PF09497 - Transcription mediator complex subunit Med12
PF12145 - Eukaryotic Mediator 12 subunit domain
PF12144 - Eukaryotic Mediator 12 catenin-binding domain

ModBase Predicted Comparative 3D Structure on Q93074
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsembl   
Protein SequenceProtein SequenceProtein Sequence   
AlignmentAlignmentAlignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000980 RNA polymerase II distal enhancer sequence-specific DNA binding
GO:0001104 RNA polymerase II transcription cofactor activity
GO:0001105 RNA polymerase II transcription coactivator activity
GO:0001190 transcriptional activator activity, RNA polymerase II transcription factor binding
GO:0003682 chromatin binding
GO:0003712 transcription cofactor activity
GO:0003713 transcription coactivator activity
GO:0005515 protein binding
GO:0008013 beta-catenin binding
GO:0008022 protein C-terminus binding
GO:0008134 transcription factor binding
GO:0019904 protein domain specific binding
GO:0030374 ligand-dependent nuclear receptor transcription coactivator activity
GO:0038023 signaling receptor activity
GO:0042809 vitamin D receptor binding
GO:0046966 thyroid hormone receptor binding
GO:0061630 ubiquitin protein ligase activity

Biological Process:
GO:0001756 somitogenesis
GO:0001843 neural tube closure
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006357 regulation of transcription from RNA polymerase II promoter
GO:0006367 transcription initiation from RNA polymerase II promoter
GO:0007492 endoderm development
GO:0007507 heart development
GO:0014003 oligodendrocyte development
GO:0014044 Schwann cell development
GO:0016567 protein ubiquitination
GO:0019827 stem cell population maintenance
GO:0021510 spinal cord development
GO:0021915 neural tube development
GO:0030178 negative regulation of Wnt signaling pathway
GO:0030518 intracellular steroid hormone receptor signaling pathway
GO:0030521 androgen receptor signaling pathway
GO:0036342 post-anal tail morphogenesis
GO:0045893 positive regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0048568 embryonic organ development
GO:0048702 embryonic neurocranium morphogenesis
GO:0060070 canonical Wnt signaling pathway
GO:0060071 Wnt signaling pathway, planar cell polarity pathway
GO:0090245 axis elongation involved in somitogenesis
GO:1990403 embryonic brain development

Cellular Component:
GO:0000151 ubiquitin ligase complex
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0016020 membrane
GO:0016592 mediator complex


-  Descriptions from all associated GenBank mRNAs
  AK302543 - Homo sapiens cDNA FLJ60974 complete cds, highly similar to Mediator of RNA polymerase II transcription subunit 12.
JD592521 - Sequence 244 from Patent WO2015022211.
JD027191 - Sequence 8215 from Patent EP1572962.
JD032477 - Sequence 13501 from Patent EP1572962.
AF117755 - Homo sapiens thyroid hormone receptor-associated protein complex component TRAP230 mRNA, complete cds.
BC156136 - Synthetic construct Homo sapiens clone IMAGE:100062449, MGC:190518 mediator complex subunit 12 (MED12) mRNA, encodes complete protein.
BC156978 - Synthetic construct Homo sapiens clone IMAGE:100062821, MGC:190621 mediator complex subunit 12 (MED12) mRNA, encodes complete protein.
AF071309 - Homo sapiens OPA-containing protein mRNA, complete cds.
D83783 - Homo sapiens mRNA for KIAA0192 gene, partial cds.
AB383789 - Synthetic construct DNA, clone: pF1KSDA0192, Homo sapiens MED12 gene for mediator of RNA polymerase II transcription, subunit 12 homolog, complete cds, without stop codon, in Flexi system.
AB102668 - Homo sapiens TNRC11 mRNA, complete cds.
FN430679 - Homo sapiens partial mRNA for putative mediator subunit 12 short (MED12S gene).
BC127264 - Homo sapiens cDNA clone IMAGE:40128482.
U80742 - Homo sapiens CAGH45 mRNA, complete cds.
BC004354 - Homo sapiens mediator of RNA polymerase II transcription, subunit 12 homolog (S. cerevisiae), mRNA (cDNA clone IMAGE:3351934), **** WARNING: chimeric clone ****.
AJ306428 - Homo sapiens partial mRNA for OPA-containing protein (HOPA gene) exon 39L, alternative splice variant.
U23863 - Human clone mcag36 chromosome 1 CAG repeat region.
JD370342 - Sequence 351366 from Patent EP1572962.
JD429073 - Sequence 410097 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q93074 (Reactome details) participates in the following event(s):

R-HSA-212352 Formation of ARC coactivator complex
R-HSA-212380 Formation of TRAP coactivator complex
R-HSA-212432 Formation of DRIP coactivator complex
R-HSA-381309 PPARG:RXRA heterodimer binds to fatty acid-like ligands
R-HSA-212436 Generic Transcription Pathway
R-HSA-381340 Transcriptional regulation of white adipocyte differentiation
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-1266738 Developmental Biology
R-HSA-74160 Gene expression (Transcription)

-  Other Names for This Gene
  Alternate Gene Symbols: ARC240, CAGH45, ENST00000374080.1, ENST00000374080.2, ENST00000374080.3, ENST00000374080.4, ENST00000374080.5, ENST00000374080.6, ENST00000374080.7, HOPA, KIAA0192, MED12_HUMAN, NM_005120, O15410, O75557, Q93074, Q9UHV6, Q9UND7, TNRC11, TRAP230, uc004dyy.1, uc004dyy.2, uc004dyy.3, uc004dyy.4, uc004dyy.5
UCSC ID: ENST00000374080.8
RefSeq Accession: NM_005120
Protein: Q93074 (aka MED12_HUMAN or T230_HUMAN)
CCDS: CCDS43970.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene MED12:
fg (MED12-Related Disorders)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.